title: The cytoprotective enzyme heme oxygenase-1 suppresses Ebola virus replication.
abstract: Ebola virus (EBOV) is the causative agent of a severe hemorrhagic fever in humans with reported case fatality rates as high as 90%. There are currently no licensed vaccines or antiviral therapeutics to combat EBOV infections. Heme oxygenase-1 (HO-1), an enzyme that catalyzes the rate-limiting step in heme degradation, has antioxidative properties and protects cells from various stresses. Activated HO-1 was recently shown to have antiviral activity, potently inhibiting the replication of viruses such as hepatitis C virus and human immunodeficiency virus. However, the effect of HO-1 activation on EBOV replication remains unknown. To determine whether the upregulation of HO-1 attenuates EBOV replication, we treated cells with cobalt protoporphyrin (CoPP), a selective HO-1 inducer, and assessed its effects on EBOV replication. We found that CoPP treatment, pre- and postinfection, significantly suppressed EBOV replication in a manner dependent upon HO-1 upregulation and activity. In addition, stable overexpression of HO-1 significantly attenuated EBOV growth. Although the exact mechanism behind the antiviral properties of HO-1 remains to be elucidated, our data show that HO-1 upregulation does not attenuate EBOV entry or budding but specifically targets EBOV transcription/replication. Therefore, modulation of the cellular enzyme HO-1 may represent a novel therapeutic strategy against EBOV infection.
authors.affiliation: Department of Pathobiological Sciences, School of Veterinary Medicine, Influenza Research Institute, University of Wisconsin-Madison, Madison, Wisconsin, USA.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Hill-Batorski
authors.forename: Peter
authors.initials: P
authors.lastname: Halfmann
authors.forename: Gabriele
authors.initials: G
authors.lastname: Neumann
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kawaoka
mesh_terms: D002460:Cell Line; D015536:Down-Regulation; D029043:Ebolavirus / Q000235:genetics / Q000502:physiology*; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D019142:Hemorrhagic Fever, Ebola / Q000201:enzymology* / Q000235:genetics / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D014779:Virus Replication
chemical_list: D051547:Heme Oxygenase-1